Hemic and Lymphatic Diseases Commons^™

Safety And Activity Of Pembrolizumab In Combination With Rituximab In Relapsed Or Refractory Follicular Lymphoma, Loretta J Nastoupil, Collin K Chin, Jason R Westin, Nathan H Fowler, Felipe Samaniego, Xiaoyun Cheng, Man Chun John Ma, Zhiqiang Wang, Fuliang Chu, Ly Dsouza, Chizobam Obi, Jennifer Mims, Lei Feng, Shouhao Zhou, Michael Green, Richard Eric Davis, Sattva S Neelapu

Faculty, Staff and Student Publications

PD-1 blockade enhances the function of antitumor T cells and antibody-dependent, cell-mediated cytotoxicity (ADCC) of NK cells. In a single-center, open-label, phase 2 trial, we tested the combination of pembrolizumab, an anti-PD-1 monoclonal antibody, and rituximab, an anti-CD20 monoclonal antibody that induces ADCC, in 30 patients with follicular lymphoma (FL) with rituximab-sensitive disease who had relapsed after ≥1 prior therapy. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 16 cycles, and rituximab was given at 375 mg/m2 IV weekly for 4 weeks in cycle 1 only. The most common grade 3/4 adverse events (AEs) were …

Activation Of Ras/Mapk Pathway Confers Mcl-1 Mediated Acquired Resistance To Bcl-2 Inhibitor Venetoclax In Acute Myeloid Leukemia, Qi Zhang, Bridget Riley-Gillis, Lina Han, Yannan Jia, Alessia Lodi, Haijiao Zhang, Saravanan Ganesan, Rongqing Pan, Sergej N Konoplev, Shannon R Sweeney, Jeremy A Ryan, Yulia Jitkova, Kenneth Dunner, Shaun E Grosskurth, Priyanka Vijay, Sujana Ghosh, Charles Lu, Wencai Ma, Stephen Kurtz, Vivian R Ruvolo, Helen Ma, Connie C Weng, Cassandra L Ramage, Natalia Baran, Ce Shi, Tianyu Cai, Richard Eric Davis, Venkata L Battula, Yingchang Mi, Jing Wang, Courtney D Dinardo, Michael Andreeff, Jeffery W Tyner, Aaron Schimmer, Anthony Letai, Rose Ann Padua, Carlos E Bueso-Ramos, Stefano Tiziani, Joel Leverson, Relja Popovic, Marina Konopleva

Faculty, Staff and Student Publications

Despite high initial response rates, acute myeloid leukemia (AML) treated with the BCL-2-selective inhibitor venetoclax (VEN) alone or in combinations commonly acquires resistance. We performed gene/protein expression, metabolomic and methylation analyses of isogenic AML cell lines sensitive or resistant to VEN, and identified the activation of RAS/MAPK pathway, leading to increased stability and higher levels of MCL-1 protein, as a major acquired mechanism of VEN resistance. MCL-1 sustained survival and maintained mitochondrial respiration in VEN-RE cells, which had impaired electron transport chain (ETC) complex II activity, and MCL-1 silencing or pharmacologic inhibition restored VEN sensitivity. In support of the importance …

Cilia Proteins Are Biomarkers Of Altered Flow In The Vasculature, Ankan Gupta, Karthikeyan Thirugnanam, Madhan Thamilarasan, Ashraf M. Mohieldin, Hadeel T. Zedan, Shubhangi Prabhudesai, Meghan R. Griffin, Andrew D. Spearman, Amy Pan, Sean P. Palecek, Huseyin C. Yalcin, Surya M. Nauli, Kevin R. Rarick, Rahima Zennadi, Ramani Ramchandran

Pharmacy Faculty Articles and Research

Cilia, microtubule-based organelles that project from the apical luminal surface of endothelial cells (ECs), are widely regarded as low-flow sensors. Previous reports suggest that upon high shear stress, cilia on the EC surface are lost, and more recent evidence suggests that deciliation—the physical removal of cilia from the cell surface—is a predominant mechanism for cilia loss in mammalian cells. Thus, we hypothesized that EC deciliation facilitated by changes in shear stress would manifest in increased abundance of cilia-related proteins in circulation. To test this hypothesis, we performed shear stress experiments that mimicked flow conditions from low to high shear stress …

Effective Therapy For Aml With Runx1 Mutation By Cotreatment With Inhibitors Of Protein Translation And Bcl2, Christopher P Mill, Warren Fiskus, Courtney D Dinardo, Christine Birdwell, John A Davis, Tapan M Kadia, Koichi Takahashi, Nicholas Short, Naval Daver, Maro Ohanian, Gautam Borthakur, Steven M Kornblau, Michael R Green, Yuan Qi, Xiaoping Su, Joseph D Khoury, Kapil N Bhalla

Faculty, Staff and Student Publications

The majority of RUNX1 mutations in acute myeloid leukemia (AML) are missense or deletion-truncation and behave as loss-of-function mutations. Following standard therapy, AML patients expressing mtRUNX1 exhibit inferior clinical outcome than those without mutant RUNX1. Studies presented here demonstrate that as compared with AML cells lacking mtRUNX1, their isogenic counterparts harboring mtRUNX1 display impaired ribosomal biogenesis and differentiation, as well as exhibit reduced levels of wild-type RUNX1, PU.1, and c-Myc. Compared with AML cells with only wild-type RUNX1, AML cells expressing mtRUNX1 were also more sensitive to the protein translation inhibitor homoharringtonine (omacetaxine) and BCL2 inhibitor venetoclax. Homoharringtonine treatment repressed …

Epigenetic Silencing Of Tumor Suppressor Lncrna Nkila: Implication On Nf-Κb Signaling In Non-Hodgkin’S Lymphoma, Min-Yue Zhang, George Calin, Ming-Dan Deng, Rex K H Au-Yeung, Lu-Qian Wang, Chor-Sang Chim

Faculty, Staff and Student Publications

The long non-coding RNA (lncRNA) NKILA, localized to 20q13.31, is a negative regulator of NF-κB signaling implicated in carcinogenesis. As a CpG island is embedded in the promoter region of NKILA, it is hypothesized as a tumor suppressor lncRNA silenced by promoter DNA methylation in non-Hodgkin’s lymphoma (NHL). By pyrosequencing-verified methylation-specific PCR, NKILA methylation was detected in 1/10 (10%) NHL cell lines, but not in normal peripheral blood buffy coats or tonsils. NKILA methylation correlated with the repression of NKILA in cell lines. Hypomethylation treatment with 5-Aza-2′-deoxycytidine resulted in promoter demethylation and the re-expression of NKILA. In 102 …

High Risk Newly Diagnosed Multiple Myeloma, Phebe Abraham, Cassie Robertson, Aswin Srinivasan, Murtaza N. Bhuriwala, Shan Guo

Gulf Coast Division GME Research Day 2022

No abstract provided.

Splenectomy In A Patient With Von Willebrand Disease And Itp. Hemostatic Challenges, Perioperative Resuscitation, Resource Allocation And Challenges Of Management In A Regional L1 Center, Taylor Locklear, Akash Patel, Saptarshi Biswas

South Atlantic Division GME Research Day 2022

No abstract provided.

Kikuchi-Fujimoto Disease Complicated By Rheumatoid Arthritis, Type 1 Diabetes Mellitus, And Hypothyroidism, Soroush Shahrokh, Ammar Hasan, Salman Raza Alim, Michelle Hebert, Khulood Rizvi

Gulf Coast Division GME Research Day 2022

No abstract provided.

A Case Of Severe Bilateral Posterior Epistaxis Secondary To Essential Thrombocytosis, An Dao, Branden Wilson, Shan Guo, Christian Cajavilca

Gulf Coast Division GME Research Day 2022

No abstract provided.

Comorbidities, Health-Related Quality Of Life, Health-Care Utilization In Older Persons With Hemophilia-Hematology Utilization Group Study Part Vii (Hugs Vii), Randall Curtis, Marilyn Manco-Johnson, Barbara A Konkle, Roshni Kulkarni, Joanne Wu, Judith R Baker, Megan Ullman, Duc Quang Tran, Michael B Nichol

Faculty, Staff and Student Publications

PURPOSE: We compare the impact of hemophilia on comorbidities, joint problems, health-related quality of life (HRQoL) and health-care utilization between two age groups: 40-49 years and ≥50 years.

PATIENTS AND METHODS: The HUGS VII study recruited persons with hemophilia A or B age ≥40 years. Participants completed surveys to collect data on sociodemographic and clinical characteristics, hemophilia treatment regimen, pain, joint problems, comorbidities, HRQoL, depression and anxiety, at baseline and 6-months later. Clinical chart reviews documented hemophilic severity and treatment.

RESULTS: The sample includes 69 males, 65.2% aged ≥50 years, 75.4% with hemophilia A. Individuals ≥50 years were more likely …

Targeting Mcl-1 Dysregulates Cell Metabolism And Leukemia-Stroma Interactions And Resensitizes Acute Myeloid Leukemia To Bcl-2 Inhibition, Bing Z Carter, Po Yee Mak, Wenjing Tao, Marc Warmoes, Philip L Lorenzi, Duncan Mak, Vivian Ruvolo, Lin Tan, Justin Cidado, Lisa Drew, Michael Andreeff

Faculty, Staff and Student Publications

MCL-1 and BCL-2 are both frequently overexpressed in acute myeloid leukemia and critical for the survival of acute myeloid leukemia cells and acute myeloid leukemia stem cells. MCL-1 is a key factor in venetoclax resistance. Using genetic and pharmacological approaches, we discovered that MCL-1 regulates leukemia cell bioenergetics and carbohydrate metabolisms, including the TCA cycle, glycolysis and pentose phosphate pathway and modulates cell adhesion proteins and leukemia-stromal interactions. Inhibition of MCL-1 sensitizes to BCL-2 inhibition in acute myeloid leukemia cells and acute myeloid leukemia stem/progenitor cells, including those with intrinsic and acquired resistance to venetoclax through cooperative release of pro-apoptotic …

Advancing The Standard: Venetoclax Combined With Intensive Induction And Consolidation Therapy For Acute Myeloid Leukemia, Curtis A Lachowiez, Himachandana Atluri, Courtney D Dinardo

Faculty, Staff and Student Publications

The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (VEN) in combination with lower-intensity therapy is an efficacious treatment for acute myeloid leukemia (AML). VEN in combination with the hypomethylating agent azacitidine improved rates of response and measurable residual disease (MRD)-negative remissions in addition to overall survival in the pivotal phase 3 VIALE-A trial compared with azacitidine monotherapy and has since emerged as the current standard of care in older or unfit patients with AML. In younger, fit patients with AML, intensive induction and consolidation chemotherapy (IC) is commonly employed as frontline therapy; however, relapse remains the principal cause of treatment failure …

Prediction Of Early (4-Week) Mortality In Acute Myeloid Leukemia With Intensive Chemotherapy, Koji Sasaki, Tapan Kadia, Kebede Begna, Courtney D Dinardo, Gautam Borthakur, Nicholas J Short, Nitin Jain, Naval Daver, Elias Jabbour, Guillermo Garcia-Manero, Guillermo Montalban Bravo, Lucia Masarova, Sherry Pierce, Marina Konopleva, Farhad Ravandi, Ayalew Tefferi, Hagop Kantarjian

Faculty, Staff and Student Publications

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m2 during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was …

Engineered Cord Blood Megakaryocytes Evade Killing By Allogeneic T-Cells For Refractory Thrombocytopenia, Bijender Kumar, Vahid Afshar-Kharghan, Mayela Mendt, Robert Sackstein, Mark R Tanner, Uday Popat, Jeremy Ramdial, May Daher, Juan Jimenez, Rafet Basar, Luciana Melo Garcia, Mayra Shanley, Mecit Kaplan, Xinhai Wan, Vandana Nandivada, Francia Reyes Silva, Vernikka Woods, April Gilbert, Ricardo Gonzalez-Delgado, Sunil Acharya, Paul Lin, Hind Rafei, Pinaki Prosad Banerjee, Elizabeth J Shpall

Faculty, Staff and Student Publications

The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on ex-vivo expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, …

Complexities And Complications Of Extreme Obesity, Haval Ali, Udit Naik, Michelle Mcdonald, Mohammad Almosa, Karen Horn, Alexis Staines, Louis Maximilian Buja

Faculty, Staff and Student Publications

Obesity is a common chronic disorder and has detrimental long-term consequences if left untreated. Herein, we report a case of a young lady who suffered from morbid obesity and many of its consequences, and we present a literature review of these complications. While the cause of obesity is multifactorial, the genetic component is particularly important in the pathophysiology of marked obesity. Resistance to Leptin is considered one of the main causes of obesity. There is a unique relationship between polycystic ovary syndrome and obesity, as observed in our case. Obesity is associated with cardiovascular and lung diseases such as heart …

Improving Lymphedema Self-Management And Screening In Newly Diagnosed Breast Cancer Clients Through The Use Of A Self-Management Lymphedema Toolkit, Kescia Gray

Doctor of Nursing Practice (DNP) Manuscripts

Background and Significance: With breast cancer effecting women at much younger ages and modern treatments prolonging the life span, survivors are at increased risk of developing breast cancer-related lymphedema (BCRL), a chronic, progressive condition that can cause disability.

Purpose: The purpose of the project was to determine the level of knowledge and awareness of BCRL in newly diagnosed breast cancer clients; and to provided education on self-care after treatment, using of a self-management lymphedema toolkit (SMLT), to decrease risks of treatment-related lymphedema, improve self-efficacy, and enhance quality of life (QOL).

Methods: Newly diagnosed breast cancer clients (N=10) from the Breast …

Utilization Of Patient-Controlled Analgesia Reduces Length Of Stay Of Sickle Cell Crisis Hospitalizations, Brett M. Prestia, Talha Ramzan, Catherine Waldron, Ameer Malik, Robert M. Pallay, Candace R. Murbach, Mike Flynn, Eric Shaw Phd, Abdullah Kutlar, Daniel Lowe

HCA Healthcare Journal of Medicine

Background

Sickle cell crisis hospitalizations are emotionally and financially burdensome to patients and healthcare systems, and processes to decrease the frequency or length of stay of these crises should be examined.

Methods

This is a multicenter retrospective hospital record review of sickle cell crisis hospitalizations as defined by ICD-10 codes (D57.1-4), from January 2016 through December 2019, examining inpatient medication administration records and length of stay among admitted adults aged 18–65 years. Patient controlled analgesia orders using morphine, hydromorphone, fentanyl and/or merperidine at any point of an admission (n=188) were compared to admissions without any patient-controlled analgesia orders (n=2,159). The …

Occlusive Pulmonary Artery Thrombosis In A Healthy Neonate With No Identifiable Risk Factors, Cynthia Laviolette, Jason Turner, Latasha Lewis, Song-Gui Yang, Tim Pettitt, Kurt D Piggott

Faculty, Staff and Student Publications

Pulmonary artery thrombosis is reported in neonates with risk factors for hypercoagulability. No consensus exists regarding standard therapy for this condition. We present a neonate, with no risk factors for thrombosis, who was admitted after birth to the Pediatric Cardiac Intensive Care Unit with an occlusive left pulmonary artery thrombus.

Microangiopathic Haemolytic Anaemia Diagnosis And Management In Thrombotic Thrombocytopenic Purpura And Haemolytic Uraemic Syndrome: A Review, Adam P. Korneluk

International Undergraduate Journal of Health Sciences

Microangiopathic haemolytic anaemia (MAHA) describes non-immune haemolysis by intravascular fragmentation of red blood cells, resulting from microvascular thrombosis characteristic of thrombotic microangiopathy (TMA). TMA-associated MAHAs include several diseases but are mostly associated with thrombotic thrombocytopenic purpura (TTP) and haemolytic-uremic syndrome (HUS). TTP is caused by a severe deficiency in ADAMTS13 proteinase, responsible for regulating coagulation, either due to presence of anti-ADAMTS13 (acquired iTTP; immune-mediated) or mutations in ADAMTS13 itself (congenital cTTP). HUS is caused by abnormal and uncontrolled complement activation, either by bacterial toxin activity (typical dHUS) or lack of normal regulatory proteins (atypical aHUS). This review focuses on TTP …

Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021, Iujhs Full Issue

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences